PROJECT SUMMARY The long term objective of this project is to investigate the regulation of FGF signaling in lacrimal gland development, which has important implications for understanding the etiology of the diseased lacrimal gland in human. The lacrimal gland develops through a branching morphogenesis process primarily driven by FGF signaling, which itself is regulated by glycosaminoglycan in the extracellular space. This application will focus on the role of glycosaminoglycan in lacrimal gland development and determine how the glycosaminoglycan fine structure regulates FGF signaling. Specifically, mouse genetic models will be developed to test the functions of glycosaminoglycan biosynthetic genes in lacrimal gland development, biochemical assays will be performed to examine the interaction between glycosaminoglycan and FGF molecules, and finally, explant culture systems will be utilized to determine the requirement of glycosaminoglycan in FGF signaling. By investigating the regulation of FGF signaling in murine lacrimal gland, this project will both contribute to medical research in treating human congenital eye diseases and advance our understanding of the mesenchymal-epithelial interaction paradigm.